Bio-sensing and temperature-sensing integrated circuit

ABSTRACT

An integrated circuit includes two or more rows of heating elements, two or more columns of heating elements, and a plurality of sensing areas. Each sensing area is between two adjacent rows of the rows of heating elements, between two adjacent columns of the columns of heating elements, and includes a bio-sensing device and a temperature-sensing device.

PRIORITY CLAIM

The present application is a divisional of U.S. application Ser. No.14/713,365, filed May 15, 2015, which claims the priority of U.S.Provisional Application No. 62/051,622, filed Sep. 17, 2014, which areincorporated herein by reference in their entireties.

RELATED APPLICATION

U.S. application Ser. No. 14/713,365 relates to U.S. patent applicationSer. No. 14/079,703, filed Nov. 11, 2013, the disclosure of which isincorporated herein by reference in its entirety.

BACKGROUND

Modern semiconductor technology is usable for forming bioelectricaldevices that perform various types of bio-diagnosis. In someapplications, some bio tests include controlling a diagnostic sample atone or more temperatures at different time period by different stages.For example, a molecular multiplication process, also known aspolymerase chain reaction process or PCR process, includes heating asample solution to different temperatures for separatingdeoxyribonucleic acid (DNA) strands in the sample solution and forsynthesizing new DNA segments based on the separated DNA strains by aspecific primer at a specific temperature.

BRIEF DESCRIPTION OF THE DRAWINGS

Aspects of the present disclosure are best understood from the followingdetailed description when read with the accompanying figures. It isnoted that, in accordance with the standard practice in the industry,various features are not drawn to scale. In fact, the dimensions of thevarious features may be arbitrarily increased or reduced for clarity ofdiscussion.

FIG. 1 is a functional block diagram of an integrated circuit inaccordance with some embodiments.

FIG. 2A is a circuit diagram of a sensing pixel of the integratedcircuit in FIG. 1 in accordance with some embodiments.

FIG. 2B is a cross-sectional view of the sensing pixel of FIG. 2A inaccordance with some embodiments.

FIGS. 3A-3B are circuit diagrams of two adjacent sensing pixels usablein the integrated circuit in FIG. 1 in accordance with some embodiments.

FIGS. 4A-4C are block diagrams of heating elements usable in theintegrated circuit in FIG. 1 in accordance with some embodiments.

FIGS. 5A-5B are cross-sectional views of a portion of the integratedcircuit in FIG. 1 in accordance with some embodiments.

FIG. 6 is a chart of temperatures at various sensing pixels ofintegrated circuit in FIG. 5B in accordance with some embodiments.

DETAILED DESCRIPTION

The following disclosure provides many different embodiments, orexamples, for implementing different features of the invention. Specificexamples of components and arrangements are described below to simplifythe present disclosure. These are, of course, merely examples and arenot intended to be limiting. For example, the formation of a firstfeature over or on a second feature in the description that follows mayinclude embodiments in which the first and second features are formed indirect contact, and may also include embodiments in which additionalfeatures may be formed between the first and second features, such thatthe first and second features may not be in direct contact. In addition,the present disclosure may repeat reference numerals and/or letters inthe various examples. This repetition is for the purpose of simplicityand clarity and does not in itself dictate a relationship between thevarious embodiments and/or configurations discussed.

Further, spatially relative terms, such as “beneath,” “below,” “lower,”“above,” “upper” and the like, may be used herein for ease ofdescription to describe one element or feature's relationship to anotherelement(s) or feature(s) as illustrated in the figures. The spatiallyrelative terms are intended to encompass different orientations of thedevice in use or operation in addition to the orientation depicted inthe figures. The apparatus may be otherwise oriented (rotated 90 degreesor at other orientations) and the spatially relative descriptors usedherein may likewise be interpreted accordingly.

In some embodiments, an integrated circuit suitable for performingvarious types of bio-diagnosis includes an array of sensing pixels. Thearray of sensing pixels includes a mesh of heating elements insertedtherein, and each sensing pixel has a bio-sensing device and atemperature-sensing device. Moreover, in some embodiments, sensingpixels are separated by thermal isolation materials. As such, thetemperature in the proximity of each bio-sensing device is capable ofbeing locally and accurately monitored or controlled with rapidtemperature response. In some embodiments, the array of sensing pixelsis thus suitable to be configured to accommodate multiple PCR assays.

FIG. 1 is a functional block diagram of an integrated circuit 100 inaccordance with some embodiments. Integrated circuit 100 includes anarray of sensing pixels 110, which includes a plurality of sensingpixels 112[1,1], . . . , 112[M,1], . . . , 112[1,N], . . . , 112[M,N](collectively referred to as “sensing pixels 112”) arranged into Mcolumns and N rows. M and N are positive integers. In some embodiments,M ranges from 1 to 256. In some embodiments, N ranges from 1 to 256.Each sensing pixel of sensing pixels 112 of the array 110 includes asensing circuit 114 and one or more heating elements 116. Details of thesensing circuits 114 and the heating elements 116 are furtherillustrated in conjunction with FIGS. 2A-6.

Integrated circuit 100 also includes a column decoder 122 coupled withthe array of sensing pixels 110 along a column direction, a row decoder124 coupled with the array of sensing pixels 110 along a row direction,a heater driver 126 coupled with a plurality of heating elements 116 ofthe array of sensing pixels 110. Moreover, integrated circuit 100includes a first amplifier 132 and a first analog-to-digital converter(ADC) 134 configured to generate a first digital code based on thesignal at a bio-sensing output of the row decoder 124. In someembodiments, bio-sensing output includes a signal representing a resultof ion sensing or charge detection of bio-molecular interactions.Integrated circuit 100 also includes a second amplifier 142 and a secondADC 144 configured to generate a second digital code based on the signalat a temperature-sensing output of the row decoder 124. Integratedcircuit 100 further includes a control unit 150 configured to controlthe column decoder 122, the row decoder 124, and the heater driver 126,and to receive the first digital code and the second digital code.

Column decoder 122 is coupled with sensing pixels 112 and is configuredto generate a plurality of column selection signals COL[1] . . . COL[M].In some embodiments, each column selection signal COL[1] or COL[M] iscoupled with a corresponding column of sensing pixels 112.

Row decoder 124 is coupled with sensing pixels 112 through a pluralityof signal paths S[1] . . . S[N] and T[1] . . . T[N]. In someembodiments, each signal path of S[1] to S[N] is configured to receive asignal from a selected bio-sensing device of a corresponding row ofsensing pixels 112. In some embodiments, each signal path of T[1] toT[N] is configured to receive a signal from a selectedtemperature-sensing device of a corresponding row of sensing pixels 112.Row decoder 124 is also configured to generate signals at a bio-sensingoutput 124 a and a temperature-sensing output 124 b based on a selectedrow of sensing pixels 112.

Amplifier 132 is configured to receive and amplify the signal at output124 a to a voltage level suitable to be processed by ADC 134. In someembodiments, amplifier 132 is integrally formed within ADC 134. In someembodiments, amplifier 132 is omitted. In some embodiments, ADC 134 andControl unit 150 are omitted. In some embodiments, one or more sets ofthe combination of an amplifier and an ADC similar to amplifier 132 andADC 134 are added to process signals from signal paths S[1] to S[N] withamplifier 132 and ADC 134. In some embodiments, signal paths S[1] toS[N] are assigned to one of the different sets of amplifier/ADC in ahard-wired manner. In some embodiments, the load sharing among thedifferent sets of amplifier/ADC is performed in a dynamic manner.

Amplifier 142 is configured to receive and amplify the signal at output124 b to a voltage level suitable to be processed by ADC 144. In someembodiments, amplifier 142 is integrally formed within ADC 144. In someembodiments, amplifier 142 is omitted. In some embodiments, ADC 134 andControl unit 150 are omitted. In some embodiments, one or more sets ofthe combination of an amplifier and an ADC similar to amplifier 142 andADC 144 are added to process signals from signal paths T[1] to T[N] withamplifier 142 and ADC 144. In some embodiments, signal paths T[1] toT[N] are assigned to one of the different sets of amplifier/ADC in ahard-wired manner. In some embodiments, the load sharing among thedifferent sets of amplifier/ADC is performed in a dynamic manner.

FIG. 2A is a circuit diagram of a sensing pixel 200 of the integratedcircuit 100 in FIG. 1 in accordance with some embodiments. In someembodiments, sensing pixel 200 is usable as any one of the sensing pixel112 in FIG. 1.

Sensing pixel 200 includes a sensing circuit 210 and heating elements222, 224, 226, and 228 (also collectively referred to as “heatingelements 220”) surrounding sensing circuit 210. Sensing circuit 210includes a bio-sensing device 212, a first switching device 213, atemperature-sensing device 215, and a second switching device 216. Firstswitching device 213 is coupled between a first end of bio-sensingdevice 212 and a corresponding signal path of the signal paths S[1] toS[N] (FIG. 1). Second switching device 216 is coupled between a firstend of temperature-sensing device 215 and a corresponding signal path ofthe signal paths T[1] to T[N]. First switching device 213 and secondswitching device 216 are N-type transistors having gates coupled with acorresponding column selection signal COL[1] to COL[M]. A second end ofbio-sensing device 212 and a second end of temperature-sensing device215 are coupled together and configured to receive a reference voltage.In some embodiments, bio-sensing device 212 includes a nanowire or afield effect transistor. In some embodiments, temperature-sensing device215 includes a diode. In some embodiments, first switching device 213 orsecond switching device 216 is implemented by other types of switchingdevices, such as a transmission gate or a P-type transistor.

Bio-sensing device 212 is configured to generate a bio-sensing signalresponsive to an electrical characteristic of a sensing film 264 (FIG.2B). Detail description of sensing film 264 will be further provided inconjunction with FIG. 2B. First switching device 213 is configured toselectively couple bio-sensing device 212 with bio-sensing output 124 a(FIG. 1). Temperature-sensing device 215 is configured to generate atemperature-sensing signal responsive to a temperature of the sensingfilm 264. Second switching device 216 is configured to selectivelycouple temperature-sensing device 215 with temperature-sensing output124 b (FIG. 1). Heating elements 220 are configured to adjust thetemperature of the sensing film 264.

FIG. 2B is a cross-sectional view of an implementation of the sensingpixel 200 having a circuit diagram depicted in FIG. 2A in accordancewith some embodiments. Components that are the same or similar to thosedepicted in FIG. 2A are given the same reference numbers. Moreover,various structural components of sensing pixel 200 that are not shown inFIG. 2A because of the limitation of a circuit diagram are depicted inFIG. 2B.

Sensing pixel 200 includes a substrate 230, an interconnection structure240 over substrate 230, a silicon layer 250 over interconnectionstructure 240, an isolation layer 262 over silicon layer 250, sensingfilms 264 and 266 over bulk layer 250, and a micro-conduit structure 270over the sensing films 264 and 266 and isolation layer 262.

Compared with FIG. 2A, sensing circuit 210 of sensing pixel 200 isformed within silicon layer 250 under sensing films 264. Also, heatingelements 220 are formed within silicon layer 250 surrounding sensingcircuit 210. In some embodiments, signal and power paths of siliconlayer 250 are electrically routed out of silicon layer 250 by theinterconnection structure 240. In some embodiments, heating elements 220are polysilicon resistors or doped semiconductor resistors. In someembodiments, heating elements 220 are metallic resistors formed withinthe interconnection structure 240.

In some embodiments, the fabrication of sensing pixel 200 is dividedinto three stages. In the first stage, portion I of sensing pixel 200,including interconnection structure 240 and silicon layer 250, isfabricated on a semiconductor substrate (not shown). In the secondstage, the resulting semiconductor structure from the first stage isflipped and bounded onto portion II of sensing pixel 200, which includessubstrate 230. In some embodiments, substrate 230 is also referred to asa handle substrate. In the third stage, the original substrate on whichportion I is formed is removed and various components and structurescorresponding to portion III of sensing pixel 200 are formed. In someembodiments, the original substrate is a silicon-on-isolation (SOI)substrate, and some or all of the isolation layer 262 is from theoriginal SOI substrate. In some embodiments, the original substrate is anon-SOI substrate, and all components and structures corresponding toportion III of sensing pixel 200 are fabricated after the originalsubstrate is removed.

In some embodiments, substrate 230 has a thickness ranging from 50 μm to500 μm. In some embodiments, interconnection structure 240 has athickness ranging from 0.5 μm to about 20 μm. In some embodiments,interconnection structure 240 has a dielectric material includingsilicon oxide (SiO₂), silicon nitride (Si₃N₄), or other suitablematerials. In some embodiments, interconnection structure 240 has athickness equal to or greater than 0.5 μm in order to accommodate atleast one layer of conductive lines for signal routing. In someembodiments, a thicker interconnection structure 240 is usable toaccommodate more layers of conductive lines for signal routing. However,in some embodiments, when interconnection structure 240 has a thicknessgreater than 20 μm, the flatness of the interconnection structure 240becomes harder to be controlled within a predetermined tolerance duringthe fabrication process, which in turn reduces a yield rate of sensingpixel 200.

In some embodiments, silicon layer 250 has a thickness ranging from 0.05μm to 3 μm. In some embodiments, electrical characteristics of variouscomponents formed in a thinner silicon layer 250 are easier to becontrolled during the fabrication process than the counterparts in athicker silicon layer 250. In some embodiments, when silicon layer 250has a thickness greater than 3 μm, the process uniformity becomes harderto be controlled within a predetermined tolerance during the fabricationprocess. In some embodiments, when silicon layer 250 has a thicknessless than 0.05 μm, silicon layer 250 becomes easier to be physicallydamaged by mechanical stresses thereon. In some embodiments, isolationlayer 262 has a thickness ranging from 0.05 μm to 5 μm. In someembodiments, isolation layer 262 has a material including silicon oxide(SiO₂), silicon nitride (Si₃N₄), or other suitable materials. In someembodiments, when isolation layer 262 has a thickness greater than 5 μm,an aspect ratio for forming an opening (as a part of sensing region 280)becomes greater, which in turn reduces a yield rate of sensing pixel200. In some embodiments, when isolation layer 262 has a thickness lessthan 0.05 μm, isolation layer 262 does not provide sufficient protectionto the electrical components formed below isolation layer 262 from thechemicals in a sample solution to be sensed by sensing circuit 210.

Isolation layer 262 has an opening over sensing circuit 210. Sensingfilm 264 is formed in the opening over sensing circuit 210. Sensing film266 is formed on the isolation layer 262. In some embodiments, sensingfilm 266 is removed or omitted while sensing film 264 remains in theopening over sensing circuit 210. In some embodiments, sensing film 264has a material including hafnium oxide (HFO₂), SiO₂, tantalum pentoxide(Ta₂O₅), or other suitable materials. In some embodiments, sensing film264 is formed by performing a native oxidation process on top of thesilicon layer 250.

Micro-fluidic (or micro-conduit) structure 270 is formed over isolationlayer 262. Micro-fluidic structure 270, sensing films 264 and 266, andisolation layer 262 form a sensing region 280 configured to receive asample solution to be sensed by sensing circuit 210. In someembodiments, micro-conduit structure 270 has a material including SiO2,silicon nitride (Si₃N₄), or other suitable materials. In someembodiments, micro-fluidic structure 270 is fabricated by bio-compatiblematerial, such as polydimethylsiloxane (PDMS) or other types of polymeron another substrate (e.g., a glass-based substrate), and flip bondedwith the other portions of the structure 200. In some embodiments,micro-fluidic structure 270 has a thickness ranging from 0.1 μm to 100μm. In some embodiments, when micro-fluidic structure 270 has athickness greater than 100 μm, an aspect ratio for forming an opening(as a part of sensing region 280) becomes greater, which in turn reducesa yield rate of sensing pixel 200. In some embodiments, whenmicro-fluidic structure 270 has a thickness less than 0.1 μm, a distancebetween a roof portion of micro-fluidic structure 270 directly oversensing region 280 becomes too close to sensing film 264 that the roofportion of micro-fluidic structure 270 would likely to bend closer to,or even touching, sensing film 264. As a result, the fluid resistancefor injecting the sample solution into sensing region 280 becomes toolarge to allow a practical usage of sensing pixel 200. In someembodiments, sensing region 280 has a cubic volume ranging from 0.01 μm³to 1000000 μm³.

In operation, an ion concentration of the sample solution to be sensedby sensing circuit 210 is placed over sensing film 264 and changes anelectrical characteristic of sensing film 264, such as a surfacepotential and/or immobilized charges on the surface of sensing film 264.A bio-sensing device 212 (FIG. 2A) of sensing circuit 210 generates abio-sensing signal responsive to the electrical characteristic of thesensing film 264. Moreover, temperature-sensing device 215 (FIG. 2A)generates a temperature-sensing signal responsive to a temperature ofthe sensing film 264. Also, heating elements 220 are configured toadjust the temperature of the sensing film 264, which in turn adjuststhe temperature of the sampled solution in the sensing region 280.

FIG. 3A is a circuit diagram of two adjacent sensing pixels 300A and300B usable in the integrated circuit in FIG. 1 in accordance with someembodiments. Sensing pixels 300A and 300B include corresponding sensingcircuits 310 and heating elements 322. Sensing pixels 300A and 300B donot overlap with each other and do not share any of the heating elements322.

FIG. 3B is a circuit diagram of two adjacent sensing pixels 300C and300D usable in the integrated circuit in FIG. 1 in accordance with someembodiments. Sensing pixels 300C and 300D include corresponding sensingcircuits 310 and heating elements 322 and 324. Sensing pixels 300C and300D overlap with each other and have a shared heating element 324.

FIG. 4A is a block diagram of heating elements 420A usable in theintegrated circuit in FIG. 1 in accordance with some embodiments.Heating elements 420A correspond to heating elements 116 in FIG. 1.Adjacent sensing pixels in FIG. 4A have an arrangement similar toadjacent sensing pixels depicted in FIG. 3B. Other details of sensingpixels 112 and the integrated circuit 100 are omitted.

Heating elements 420A includes M+1 columns of heating elements 422[1] to422[M+1] for M columns of sensing circuits 114 (FIG. 1). Heatingelements 420A also includes N+1 rows of heating elements 424[1] to424[N+1] for N rows of sensing circuits 114. Each column of heatingelements includes heating elements coupled in series and is coupled withheater driver 126 (FIG. 1) to receive corresponding column drivingsignals HC[1] to HC[M+1]. Each row of heating elements includes heatingelements coupled in series and is also coupled with heater driver 126 toreceive corresponding row driving signals HR[1] to HR[N+1]. In someembodiments, one or more columns of the plurality of columns of heatingelements are controlled by a corresponding driving signal. For example,in some embodiments, the M+1 columns of heating elements 422[1] to422[M+1] are divided into sub-groups of columns of heating elements, andevery sub-group of columns, such as columns 422[1] and 422[2] forexample, are controlled by the same driving signal, and thus thecorresponding driving signals of each sub-group of columns, such asdriving signals HC[1] and HC[2], refer to the same driving signal. Insome embodiments, the N+1 rows of heating elements 424[1] to 424[N+1]are divided into sub-groups of rows of heating elements, and everysub-group of rows, such as rows 424[1] and 424[2] for example, arecontrolled by the same driving signal, and thus the correspondingdriving signals of each sub-group of rows, such as driving signals HR[1]and HR[2], refer to the same driving signal.

In some embodiments, each row and each column of the heating elements420A are independently controlled through corresponding driving signals.In some embodiments, all columns of heating elements 422[1] to 422[M+1]are controlled by a common driving signal. In some embodiments, all rowsof heating elements 424[1] to 424[N+1] are controlled by a commondriving signal.

In some embodiments, heating elements 420A are capable of providing auniform temperature distribution or a predetermined temperaturedistribution among the array 110. In some embodiments, the temperatureof the array 110 (FIG. 1) is controlled in a closed-loop manner that thedriving signals of heating elements 420A are generated based on thesignals from temperature-sensing devices 215 of sensing pixels of thearray 110. In some embodiments, the temperature of the array 110(FIG. 1) is controlled in an open-loop manner that the driving signalsof heating elements 420A are generated without referring to the signalsfrom temperature-sensing devices 215 of sensing pixels of the array 110.In some embodiments, the control unit 150 (FIG. 1) controls the heatingelements 420A through heater driver 126.

FIG. 4B is a block diagram of heating elements 420B usable in theintegrated circuit in FIG. 1 in accordance with some embodiments.Heating elements 420B correspond to heating elements 116 in FIG. 1.Sensing pixels in FIG. 4B have an arrangement similar to sensing pixelsdepicted in FIG. 3B. Components in FIG. 4B that are the same or similarto those in FIG. 4A are given the same reference numbers. Other detailsof sensing pixels 112 and the integrated circuit 100 are omitted.

Heating elements 420B includes M+1 columns of heating elements 422[1] to422[M+1] and N+1 rows of heating elements 424[1] to 424[N+1]. Eachsensing area corresponding to a sensing pixel to accommodate a sensingcircuit being between two adjacent rows of the rows of heating elementsand being between two adjacent columns of the columns of heatingelements. In other words, one sensing area is surrounded by two heatingelements of the rows of heating elements and two heating elements of thecolumns of heating elements. In the embodiment depicted in FIG. 4B, acolumn heating element and a row heating element corresponding to twoadjacent sides of a same sensing pixel are connected in series (depictedas having an “L” shape connection in FIG. 4B) and controlled by adriving signal. For example, one of heating elements from row 424[1] andone of heating elements from column 422[2] corresponding to a samesensing pixel are connected together and controlled by signal HP[2,1].The column 422[1] of heating elements and the row 424[N+1] of heatingelements are at the edge of the array 110 and are not grouped with anyheating elements to form “L” shape units. In the embodiment depicted inFIG. 4B, each heating element in column 422[1] and row 424[N+1] iscontrolled by an individual control signal.

As such, heating elements 420B are divided into {(M+1)×(N+1)−1} groupsof heating elements (M×N “L” shape units and M+N heating elements at theedge of the array) controlled by {(M+1)×(N+1)−1} driving signals HP[1,1]to HP[M+1,N+1] (skipping HP[1,N+1]). In some embodiments, one or moredriving signals are further grouped as the same driving signal.

In some embodiments, heating elements 420B are capable of providing auniform temperature distribution or a predetermined temperaturedistribution among the array 110. In some embodiments, the temperatureof the array 110 (FIG. 1) is controlled in a closed-loop manner that thedriving signals of heating elements 420B are generated based on thesignals from temperature-sensing devices 215 of sensing pixels of thearray 110. In some embodiments, the temperature of the array 110(FIG. 1) is controlled in an open-loop manner that the driving signalsof heating elements 420B are generated without referring to the signalsfrom temperature-sensing devices 215 of sensing pixels of the array 110.In some embodiments, the control unit 150 (FIG. 1) controls the heatingelements 420A through heater driver 126.

FIG. 4C is a block diagram of heating elements 430 usable in theintegrated circuit in FIG. 1 in accordance with some embodiments.Heating elements 430 correspond to heating elements 116 in FIG. 1.Sensing pixels in FIG. 4C have an arrangement similar to sensing pixelsdepicted in FIG. 3A. Other details of sensing pixels 112 and theintegrated circuit 100 are omitted.

Heating elements 430 includes groups of four serially-connected heatingelements 423[1,1] to 432[M,N]. Each group of heating elementssurrounding a corresponding sensing area. As such, heating elements 430are divided into M×N groups of heating elements controlled by M×Ndriving signals HC[1,1] to HC[M,N]. In some embodiments, one or moredriving signals are further grouped as the same driving signal. In someembodiments, the control unit 150 (FIG. 1) controls the heating elements430 through heater driver 126 based on the signals fromtemperature-sensing devices of sensing pixels of the array 110 in aclosed-loop manner as illustrated in conjunction with FIGS. 4A and 4B.In some embodiments, the control unit 150 controls the heating elements430 through heater driver 126 in an open-loop manner as illustrated inconjunction with FIGS. 4A and 4B.

FIG. 5A is a cross-sectional view of a portion of the integrated circuit500A in accordance with some embodiments. Integrated circuit 500Acorresponds to integrated circuit 100 in FIG. 1, and components in FIG.5A that are the same or similar to those in FIG. 2B are given the samereference numbers.

Integrated circuit 500A includes a plurality of sensing pixels 511, 513,515, 517, and 519 over substrate 230. Each sensing pixel of sensingpixels 511, 513, 515, 517, and 519 has a corresponding sensing circuit210 surrounded by a corresponding heating element 220 as illustrated inconjunction with FIG. 2B. Micro-conduit structure 270 is formed overisolation layer 262. Micro-conduit structure 270, sensing films 264 and266, and isolation layer 262 form a combined sensing region 520configured to receive a sample solution to be sensed by sensing pixels511, 513, 515, 517, and 519. Compared with sensing region 280, sensingregion 520 exposes sensing film 264 corresponding to more than onesensing pixels 511, 513, 515, 517, and 519.

Only a row of five sensing pixels 511, 513, 515, 517, and 519 isdepicted in FIG. 5A. In some embodiments, micro-conduit structure 270and isolation layer 262 divide the array 110 in FIG. 1 into two or moresensing regions 280 or 520, where each region exposes sensing filmportion(s) corresponding to a predetermined number of sensing pixels112. For example, sensing region 280 in FIG. 2B is configured to exposethe sensing film portion of one sensing pixel, and sensing region 520 inFIG. 5A is configured to expose the sensing film portions of fivesensing pixels. As such, an integrated circuit 100 is capable of beingused to form a testing device that has two or more sensing regions. Insome embodiments, micro-conduit structure 270 and isolation layer 262form a single sensing region based on the array 110, where the singlesensing region exposes the sensing film portions corresponding to all ora predetermined number of sensing pixels 112.

FIG. 5B is a cross-sectional view of a portion of the integrated circuit500B in accordance with some embodiments. Integrated circuit 500Bcorresponds to integrated circuit 100 in FIG. 1. Components in FIG. 5Bthat are the same or similar to those in FIG. 5A and FIG. 2B are giventhe same reference numbers.

Integrated circuit 500B includes a plurality of sensing pixels 532, 534,and 536 over substrate 230. Each sensing pixel of sensing pixels 532,534, and 536 has a corresponding sensing circuit 210 surrounded by acorresponding heating element 220 as illustrated in conjunction withFIG. 2B. Micro-conduit structure 270 is formed over isolation layer 262.Micro-conduit structure 270, sensing films 264 and 266, and isolationlayer 262 form three corresponding sensing regions 542, 544, and 546configured to receive three different sample solutions to be sensed bysensing circuits 210 of individual sensing pixels 532, 534, and 536.

In the embodiment depicted in FIG. 5B, a distance D₁ between the sensingcircuit 210 of sensing pixel 532 and a heating element 220 of sensingpixel 532 is less than 5 μm. A distance D₂ between the sensing circuit210 of sensing pixel 534 and the heating element 220 sensing pixel 532is 20 μm. A distance D₃ between the sensing circuit 210 of sensing pixel534 and the sensing circuit 210 of sensing pixel 536 is 400 μm.

In some bio applications using circuit 500B, a thermal time constant τis governed by equation (1), where parameters ρ, Cp, and A are density,specific heat, and surface area of the sample solution. ΔT in (1) istemperature difference when the heating power is applied.

$\begin{matrix}{\tau = \frac{\rho\; c_{p}V\;\Delta\; T}{q^{''}A}} & (1)\end{matrix}$

In some embodiments, distances D₁, D₂, and D₃ have values different formthe example in the present disclosure. In some embodiments, distancesD₁, D₂, and D₃ are set to render sensing pixels 532, 534, and 536 tohave predetermined temperatures within a predetermined temperatureaccuracy.

FIG. 6 is a chart of temperatures at various sensing pixels ofintegrated circuit in FIG. 5B in accordance with some embodiments. Inthis embodiment, a temperature accuracy of 0.64° C. is attained by2-point calibration from 25° C. to 100° C. Sensing region 542 is heatedto 100° C. with 20 mW of power while keeping thermal coupling to sensingregion 546 within 0.5%. Sensing region 544 has about 60% of thetemperature increase of sensing region 542. The response time (includingheating and cooling) achieved is about 0.35˜350 msec/K, which dependingon sample volume from several μL to sub-μL.

In some embodiments, an integrated circuit includes two or more rows ofheating elements, two or more columns of heating elements, and aplurality of sensing areas. Each sensing area of the plurality ofsensing areas is between two adjacent rows of the rows of heatingelements and is between two adjacent columns of the columns of heatingelements. Each sensing area of the plurality of sensing areas includes abio-sensing device and a temperature-sensing device. In someembodiments, one or more rows of the rows of heating elements iscontrollable by a corresponding driving signal. In some embodiments, oneor more columns of the columns of heating elements is controllable by acorresponding driving signal. In some embodiments, one sensing area ofthe plurality of sensing areas is surrounded by two heating elements ofthe rows of heating elements and two heating elements of the columns ofheating elements, and the two heating elements of the rows of heatingelements and the two heating elements of the columns of heating elementsare controllable by a driving signal. In some embodiments, one sensingarea of the plurality of sensing areas is surrounded by two heatingelements of the rows of heating elements and two heating elements of thecolumns of heating elements, and the two heating elements of the rows ofheating elements and the two heating elements of the columns of heatingelements are controllable by two or more driving signals. In someembodiments, the integrated circuit further includes a row decoderconfigured to generate signals at a bio-sensing output and atemperature-sensing output based on the bio-sensing devices and thetemperature-sensing devices of a selected row of the plurality ofsensing areas, a column decoder configured to generate a plurality ofcolumn selection signals, a first ADC configured to generate a firstdigital code based on the signal at the bio-sensing output, and a secondADC configured to generate a second digital code based on the signal atthe temperature-sensing output, and each sensing area of the pluralityof sensing areas further includes a first switching device coupledbetween the bio-sensing device and the row decoder, the first switchingdevice being controllable by a corresponding one of the plurality ofcolumn selection signals, and a second switching device coupled betweenthe temperature-sensing device and the row decoder, the second switchingdevice being controllable by the corresponding one of the plurality ofcolumn selection signals. In some embodiments, the integrated circuitfurther includes an isolation layer over the rows of heating elementsand the columns of heating elements, the isolation layer including oneor more openings, each of the one or more openings exposing an exclusivesubset of the plurality of sensing areas.

In some embodiments, an integrated circuit includes two or more rows ofheating elements, two or more columns of heating elements, and aplurality of sensing areas. Each sensing area of the plurality ofsensing areas is between two adjacent rows of the rows of heatingelements and between two adjacent columns of the columns of heatingelements. A control unit is configured to receive a first digital codebased on a plurality of bio-sensing signals corresponding to theplurality of sensing areas, and a second digital code based on aplurality of temperature-sensing signals corresponding to the pluralityof sensing areas. In some embodiments, the integrated circuit furtherincludes a heater driver, wherein the control unit is configured tocontrol the rows of heating elements and the columns of heating elementsthrough the heater driver based on the second digital code. In someembodiments, the integrated circuit further includes a heater driver,wherein the control unit is configured to control the rows of heatingelements and the columns of heating elements through the heater driverin an open-loop manner. In some embodiments, the control unit isconfigured to select a subset of the plurality of bio-sensing signalsbased on a plurality of selection signals, and the first digital code isbased on the subset of the plurality of bio-sensing signals. In someembodiments, the plurality of selection signals further selects a subsetof the plurality of temperature-sensing signals, and the second digitalcode is based on the subset of the plurality of temperature-sensingsignals. In some embodiments, the plurality of sensing areas includes anarray of M×N sensing areas, the two or more columns of heating elementsinclude M+1 columns of heating elements, and the two or more rows ofheating elements include N+1 rows of heating elements. In someembodiments, the plurality of sensing areas includes an array of M×Nsensing areas, the two or more columns of heating elements include M×2columns of heating elements, and the two or more rows of heatingelements include N×2 rows of heating elements.

In some embodiments, an integrated circuit includes two or more rows ofheating elements, two or more columns of heating elements, and aplurality of sensing circuits, each sensing circuit of the plurality ofsensing circuits being between two adjacent rows of the rows of heatingelements and between two adjacent columns of the columns of heatingelements, in a same silicon layer as the rows of heating elements andthe columns of heating elements, and configured to generate abio-sensing signal and a temperature-sensing signal. In someembodiments, the integrated circuit further includes a sensing filmoverlying the silicon layer, wherein each sensing circuit of theplurality of sensing circuits includes a sensing device configured togenerate the bio-sensing signal responsive to an electricalcharacteristic of the sensing film. In some embodiments, the integratedcircuit further includes an isolation layer overlying the silicon layer,wherein the isolation layer divides the sensing film into two or moresensing film portions, each sensing film portion corresponding to apredetermined number of sensing circuits. In some embodiments, theintegrated circuit further includes a micro-fluidic structure overlyingthe isolation layer and the sensing film portions. In some embodiments,the integrated circuit further includes an isolation layer overlying thesilicon layer, and a micro-fluidic structure overlying the isolationlayer and the sensing film, wherein the micro-fluidic structure, theisolation layer, and an entirety of the plurality of sensing circuitsform a single sensing region. In some embodiments, the silicon layeroverlies an interconnection structure, the interconnection structureincluding power paths configured to electrically route driving signalscorresponding to the rows of heating elements and columns of heatingelements, and signal paths configured to electrically route thebio-sensing signals and temperature-sensing signals generated by theplurality of sensing circuits.

The foregoing outlines features of several embodiments so that thoseskilled in the art may better understand the aspects of the presentdisclosure. Those skilled in the art should appreciate that they mayreadily use the present disclosure as a basis for designing or modifyingother processes and structures for carrying out the same purposes and/orachieving the same advantages of the embodiments introduced herein.Those skilled in the art should also realize that such equivalentconstructions do not depart from the spirit and scope of the presentdisclosure, and that they may make various changes, substitutions, andalterations herein without departing from the spirit and scope of thepresent disclosure.

What is claimed is:
 1. An integrated circuit comprising: two or morerows of heating elements; two or more columns of heating elements; aplurality of sensing areas, each sensing area of the plurality ofsensing areas being between two adjacent rows of the rows of heatingelements and being between two adjacent columns of the columns ofheating elements; and a control unit configured to receive: a firstdigital code based on a plurality of bio-sensing signals correspondingto the plurality of sensing areas; and a second digital code based on aplurality of temperature-sensing signals corresponding to the pluralityof sensing areas.
 2. The integrated circuit of claim 1, furthercomprising a heater driver, wherein the control unit is configured tocontrol the rows of heating elements and the columns of heating elementsthrough the heater driver based on the second digital code.
 3. Theintegrated circuit of claim 1, further comprising a heater driver,wherein the control unit is configured to control the rows of heatingelements and the columns of heating elements through the heater driverin an open-loop manner.
 4. The integrated circuit of claim 1, whereinthe control unit is configured to select a subset of the plurality ofbio-sensing signals based on a plurality of selection signals, and thefirst digital code is based on the subset of the plurality ofbio-sensing signals.
 5. The integrated circuit of claim 4, wherein theplurality of selection signals further selects a subset of the pluralityof temperature-sensing signals, and the second digital code is based onthe subset of the plurality of temperature-sensing signals.
 6. Theintegrated circuit of claim 1, wherein the plurality of sensing areascomprises an array of M×N sensing areas, the two or more columns ofheating elements comprise M+1 columns of heating elements, and the twoor more rows of heating elements comprise N+1 rows of heating elements.7. The integrated circuit of claim 1, wherein the plurality of sensingareas comprises an array of M×N sensing areas, the two or more columnsof heating elements comprise M×2 columns of heating elements, and thetwo or more rows of heating elements comprise N×2 rows of heatingelements.
 8. An integrated circuit, comprising: two or more rows ofheating elements; two or more columns of heating elements; a pluralityof sensing areas, each sensing area of the plurality of sensing areas:being between two adjacent rows of the rows of heating elements; beingbetween two adjacent columns of the columns of heating elements; andcomprising a bio-sensing device configured to generate a bio-sensingsignal and a temperature-sensing device configured to generate atemperature-sensing signal, the plurality of sensing areas thereby beingconfigured to generate a plurality of bio-sensing signals and aplurality of temperature-sensing signals; and a control unit configuredto receive a first digital code based on the plurality of bio-sensingsignals and a second digital code based on the plurality oftemperature-sensing signals.
 9. The integrated circuit of claim 8,wherein, for each sensing area of the plurality of sensing areas, thebio-sensing device is configured to generate the bio-sensing signalresponsive to an electrical characteristic of a sensing film, and thetemperature-sensing device is configured to generate thetemperature-sensing signal responsive to a temperature of the sensingfilm.
 10. The integrated circuit of claim 9, wherein the control unit isconfigured to adjust the temperature of the sensing film by controllingat least one heating element of the two or more rows of heating elementsand two or more columns of heating elements.
 11. The integrated circuitof claim 8, further comprising: a plurality of first signal paths, eachfirst signal path of the plurality of first signal paths configured toreceive a subset of the plurality of bio-sensing signals from acorresponding row of sensing areas of the plurality of sensing areas;and a plurality of second signal paths, each second signal path of theplurality of second signal paths configured to receive a subset of theplurality of temperature sensing signals from a corresponding row ofsensing areas of the plurality of sensing areas.
 12. The integratedcircuit of claim 11, further comprising a row decoder configured to:generate, at a bio-sensing output, a first signal based on the subset ofthe plurality of bio-sensing signals corresponding to a selected row ofsensing areas of the plurality of sensing areas, and generate, at atemperature-sensing output, a second signal based on the subset of theplurality of temperature-sensing signals corresponding to the selectedrow of sensing areas of the plurality of sensing areas.
 13. Theintegrated circuit of claim 12, further comprising: a first amplifierand analog-to-digital converter (ADC) set configured to receive thefirst signal and generate the first digital code; and a second amplifierand ADC set configured to receive the second signal and generate thesecond digital code.
 14. The integrated circuit of claim 13, wherein thefirst amplifier and ADC set is one first amplifier and ADC set of aplurality of first amplifier and ADC sets configured to process theplurality of bio-sensing signals, and/or the second amplifier and ADCset is one second amplifier and ADC set of a plurality of secondamplifier and ADC sets configured to process the plurality oftemperature-sensing signals.
 15. An integrated circuit comprising: twoor more rows of heating elements; two or more columns of heatingelements; a heater driver coupled with the two or more rows of heatingelements and the two or more columns of heating elements; a plurality ofsensing areas, each sensing area of the plurality of sensing areas beingbetween two adjacent rows of the rows of heating elements and beingbetween two adjacent columns of the columns of heating elements; and acontrol unit configured to: control a temperature distribution of thetwo or more rows of heating elements and the two or more columns ofheating elements through the heater driver; receive a first digital codebased on a plurality of bio-sensing signals corresponding to theplurality of sensing areas; and receive a second digital code based on aplurality of temperature-sensing signals corresponding to the pluralityof sensing areas.
 16. The integrated circuit of claim 15, wherein therows of heating elements are configured to receive a plurality of rowdriving signals from the heater driver, and the columns of heatingelements are configured to receive a plurality of column driving signalsfrom the heater driver.
 17. The integrated circuit of claim 16, whereinat least one row driving signal of the plurality of row driving signalsis configured to control two or more rows of the rows of heatingelements, and/or at least one column driving signal of the plurality ofcolumn driving signals is configured to control two or more columns ofthe columns of heating elements.
 18. The integrated circuit of claim 15,wherein, for each sensing area of the plurality of sensing areas, aheating element group of a corresponding plurality of heating elementgroups comprises a heating element of one of the two adjacent rows ofthe rows of heating elements connected in series with a heating elementof one of the two adjacent columns of the columns of heating elements,and the plurality of heating element groups is configured to receive aplurality of driving signals from the heater driver.
 19. The integratedcircuit of claim 18, wherein the plurality of sensing areas are arrangedin rows and columns, the rows comprising an edge row and the columnscomprising an edge column, for each sensing area of the plurality ofsensing areas in the edge row, a heating element of the other one of thetwo adjacent rows of the rows of heating elements is configured toreceive an individual control signal from the heater driver, and foreach sensing area of the plurality of sensing areas in the edge column,a heating element of the other one of the two adjacent columns of thecolumns of heating elements is configured to receive an individualcontrol signal from the heater driver.
 20. The integrated circuit ofclaim 18, wherein at least one driving signal of the plurality ofdriving signals is configured to control two or more heating elementgroups of the plurality of heating element groups.